Time Bomb? The Clinical Trial ‘Gold Rush’ In India
12 CommentsBy Ed Silverman // December 18th, 2008 // 3:42 pm
The race to test drugs in India, where costs are lower and patients are plentiful, is creating a vast cottage industry of doctors and contract research operators, but a dearth of oversight and ethical standards. The result is a breeding ground for corruption and danger, according to The St. Petersberg Times, which has just run a series of stories on the topic.
In the main story, the paper’s Kris Hundley writes that, in the past three years, the FDA has inspected just eight of the thousands of trial sites in India. Meanwhile, the number of registered clinical trials being conducted in India has nearly doubled in the past year, to more than 800 ongoing or completed, according to www.clinicaltrials.gov.
On the ground in India, it is impossible to find anyone running, monitoring or auditing clinical trials who is not on the payroll of the drug makers, the paper writes, adding that doctors are paid according to the number of patients they enroll. Local ethics boards, set up to ensure patient safety, are often comprised of colleagues who approve each others’ projects and blackball naysayers…
Contract research organizations keep tabs on trials with regular audits. Site management organizations put an extra set of eyes in the doctor’s office. Both entities dangle promises of FDA-ready studies in half the time, at 30 to 60 percent the cost in the US. The secret? Cheap help and fast patient recruiting, according to the Times.
Quintiles, the world’s largest contract research organization, boasts of enrolling 50 patients with diabetes in one month in India and 204 infants for a vaccine study in three days, far faster than possible in the US, the Times writes, and notes that, in a brochure, Quintiles sums up India’s allure: ‘It’s practically a paradise for conducting clinical trials.’
Everybody wants a piece of an industry estimated to top $1 billion by 2010. But as a gold-rush mentality grips India’s booming clinical trial business, even its proponents are having second thoughts, the Times continues. Take Arun Bhatt, a physician and president of Clininvent, a contract research organization in Mumbai that is running 11 trials involving 1,000 patients. He worries Indian doctors ignore patient reactions to experimental meds, missing critical clues about a drug’s safety.
“Most sites are not used to recognizing serious adverse events, so they are underreported,” he tells the paper. “Either they don’t recognize, don’t realize or are afraid to report this information.”
In the burgeoning clinical trial business, says Amar Jesani, a doctor and medical ethicist in Mumbai, every layer of oversight is compromised by cash, and independent monitoring is nonexistent. “We’re sitting on a time bomb that may explode at any time,” he tells the paper.
India’s top drug regulator, Surinder Singh, says the FDA is training 24 Indian officials to conduct random audits of trial sites, to begin as soon as this month. His predecessors made similar promises of imminent inspections, which went unfulfilled, in 2006 and again in 2007. Meanwhile, he has rolled out the welcome mat for foreign drugmakers, promising to review applications in two to six weeks and push his ossified operation, as he put it, “from the Stone Age to the Clone Age.”
But CM Gulhati, editor of an Indian medical journal, Monthly Index of Medical Specialties, says authorities cannot cope with the tsunami of trials. “India’s drugs controller general’s office is both understaffed and incompetent,” he tells the paper, citing a case where the agency claimed it reviewed an 800-page trial protocol in just five days. “How is that even possible?”
Gulhati, who fights unbridled drug testing from a dim and cluttered office above a busy Delhi shopping plaza, reeled off several troubled trials: In 2003 in Hyderabad, an unregistered study of a heart attack drug that resulted in six deaths; in 2004 in Delhi, a first-in-human trial of a new suturing device on 13 patients without regulators’ approval.
Last year, India’s decision to become the only nation to allow domestic Sun Pharmaceutical to market the anticancer drug Letrozole for infertility in women despite warnings from Novartis, which developed the drug, that it may cause fetal harm and should be used only in postmenopausal women. And in October in Bangalore, the death of a baby during the testing of a new Wyeth vaccine.
“It’s a total farce,” Gulhati tells the paper, adding that he could not think of a single case of an Indian doctor disciplined for mishandling a trial. “When I complain people have broken the law, they ask ‘What harm have I done?’ ”
Here is the main story; a sidebar about deaths in a hospital; various patients stories;
Justice in Michigan
Do we know whether any companies, in particular, are especially capitalizing on work with these Indian cros?
pharmavet
I’ve been doing clinical trials for 25 years, both US and ex-US. Here’s my experience:
1) for an American drug company, doing ex-US trials in non UK countries can be a “pay to play” deal. You must ante up by paying an exorbitant fee to obtain product liability insurance, even if you are self-insured. Depending on the size of the program, this may amount to hundreds of thousands of dollars just to get into the country.
2) many ex-US countries do not require an IND, so that you can just jump in to trials with little or no preclinical safety data.
3) Access to investigators may need to go through a middle man, whose palms need to be greased.
4) Informed consents are not required to be translated by a certified translator.
5) Although major CRO’s are “international” in nature, the ex-US monitoring capabilities in many cases are much thinner than in US. In some cases there may only be 1-2 monitors for an entire country.
These are just a few of the problems. There are many others.
nipsey russell
patient safety is of the utmost importance in clinical trials and the indian government should put money into ensuring compliance. They should have more money since all this brings revenue and taxes into the country.
However, just a couple nits to pick here:
“On the ground in India, it is impossible to find anyone running, monitoring or auditing clinical trials who is not on the payroll of the drug makers”
Well….yes…but who else is going to pay to run the study? the St Petersburg Times? you? me?
“doctors are paid according to the number of patients they enroll”
well….yes…but how else would they be paid? more specifically they are often paid by procedure, but this somewhat means the same thing. The more subjects they enroll, the more work they take on on behalf of those footing the bills. Care should be taken to ensure that compensation doesn’t incent inappropriate enrollment, but it will always be tied to the amount of labor and resources needed to perform the duties which increases with # subjects.
nipsey russell
PV: re how many people the major CROs have in developing countries - this may be tru in smaller Asia/LatAm/E Europe countries, but all the majors now have quite a few people in India, at least double digits.
JIM: what exactly do you mean by your question. There are global CROs in India and then there are local Indian CROs. Quality and # qualified people in-country vary greatly across both categories. I noticed, a few years back, when this started to take off, that the major CROs started to build out capabilities in India, but also dozens and dozens of new CROs started up in-country. Most of these I wouldnt touch with a ten foot pole as they had just a handful of people, no institutional experience, and were just after the next hot market. That said there are a few good companies in that mix who have built up good organizations. This goes back a year or two, so things may have changed quite a bit…
riv
This is great work from the St. Peteerberg Times.
Thanks for bringing it to us, Ed.
Tom
This two part series from the St. Petersberg Times deserves an award. Pharma, once again, blames someone else. It’s “The Constant Gardner” times ten.
Justice in Michigan
Back up the line, I was wondering whether some companies, more than others, make use of the services of these cros.
In the meantime, a number of us probably saw the ABC News piece last night about the number of impoverished Americans who are going into clincial trials or surrogacy as a way to financially survive.
nipsey russell
Tom: constant gardener was fiction. no one is MURDERING anyone here, and certainly not “times ten”. that is ridiculous. all of us can agree that safety is of the utmost concern, and oversight should be tight, but lets not go overboard. also, lets not forget that these countries might actually benefit from this…and some of these people are getting access to medicines they would otherwise not have a shot at. wasnt it india where there was recent outrage over the kids dying in a clinical trial…..but it turned out the dead kids were the ones NOT getting the experimental meds and relying on standard of care??
JIM: right, i think i was focused on the “these CROs” part as that can mean quite different things. I think you will find that the use of CROs in India will depend on many factors. If there is a large pharma who doesnt have a large presence in India, then you can guess that they are probably still doing research and using a CRO there. Even if they have a large presence, they may need to use CROs if they have very large studies going on that their folks cant ramp up for. I have some idea of who is doing what, but dont feel like being specific.
riv
Constant Gardener was not fiction. It was a true story with fictional aspects to keep the movie company lawyers happy.
Salmon
I believe that even without an IND they still have to meet certain standards to be able to be used in a submission to the FDA, but I would need to check the exact language.
Even so I don’t like the potential for fraud and abuse even with the large international CROs. Remember Ketek had problems and it was run by a large CRO whose CEO was the ex-CEO of Glaxo. Plus Businessweek had an article I believe in Jan 2007 on how India was the country that US business people hated doing business with the most due to the extent of thte corruption. Surely not a good sign for obtaining valid information and protecting patients.
Salmon
nipsey russell
“Constant Gardener was not fiction. It was a true story with fictional aspects to keep the movie company lawyers happy.”
!!!!! please do tell us the real-life basis of this “true story”!
Surrogacy in India
Your blog keeps getting better and better! Your older articles are not as good as newer ones you have a lot more creativity and originality now keep it up!